P1060: NNRTI-Based vs. PI-Based ART in Infants Exposed/Not Exposed to NVP for PMTCT - New England Journal of Medicine 2010 publication

Background: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. Methods: We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. Results: A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. Conclusions: Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required.

背景：单剂量奈韦拉平（single-dose nevirapine）是资源有限地区人类免疫缺陷病毒（human immunodeficiency virus, HIV）母婴传播预防方案的核心用药，但对于经预防仍发生感染的母亲与儿童，奈韦拉平常诱导筛选出耐药病毒。此前曾暴露于单剂量奈韦拉平的儿童的最优抗逆转录病毒治疗策略目前仍不明确。
方法：我们在六个非洲国家开展了一项随机对照试验，纳入符合世界卫生组织（World Health Organization, WHO）治疗指征、年龄为6至36月龄的HIV感染儿童，对比初始治疗采用齐多夫定（zidovudine）联合拉米夫定（lamivudine）加奈韦拉平，或联合利托那韦增效洛匹那韦（ritonavir-boosted lopinavir）的疗效。本分析针对曾暴露于单剂量奈韦拉平预防用药的队列展开。研究主要终点为第24研究周时出现病毒学失败或终止治疗。基于数据与安全监查委员会的建议，该队列的入组工作提前终止。
结果：本队列共纳入164名儿童，其CD4+淋巴细胞中位数百分比为19%；其中56%的儿童处于WHO临床分期3或4期。奈韦拉平组达到主要终点的儿童比例显著高于利托那韦增效洛匹那韦组（39.6% vs. 21.7%；加权差值为18.6个百分点，95%置信区间3.7~33.6，名义P=0.02）。148名儿童中18名（12%）检出奈韦拉平基线耐药，且该基线耐药可预测治疗失败。两组不良事件发生率无显著组间差异。
结论：对于曾因HIV围产期传播预防接受单剂量奈韦拉平暴露的儿童，齐多夫定联合拉米夫定加用利托那韦增效洛匹那韦的抗逆转录病毒治疗方案，临床结局优于齐多夫定联合拉米夫定加用奈韦拉平的方案。鉴于奈韦拉平在资源有限地区同时用于HIV感染的治疗与围产期母婴传播预防，亟需开发新型HIV母婴传播预防策略以及HIV感染治疗方案。